Dredge, K.Brennan, T.Hammond, E.Lickliter, J.Lin, L.Bampton, D.Handley, P.Lankesheer, F.Morrish, G.Yang, Y.Brown, M.Millward, M.2018-09-052018-09-052018British Journal of Cancer, 2018; 118(8):1035-10410007-09201532-1827http://hdl.handle.net/2440/114176Background: PG545 (pixatimod) is a novel immunomodulatory agent, which has been demonstrated to stimulate innate immune responses against tumours in preclinical cancer models. Methods: This Phase I study investigated the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of PG545 monotherapy. Escalating doses of PG545 were administered to patients with advanced solid malignancies as a weekly 1-h intravenous infusion. Results: Twenty-three subjects were enrolled across four cohorts (25, 50, 100 and 150 mg). Three dose-limiting toxicities (DLTs)—hypertension (2), epistaxis (1)—occurred in the 150 mg cohort. No DLTs were noted in the 100 mg cohort, which was identified as the maximum-tolerated dose. No objective responses were reported. Best response was stable disease up to 24 weeks, with the disease control rate in evaluable subjects of 38%. Exposure was proportional up to 100 mg and mean half-life was 141 h. The pharmacodynamic data revealed increases in innate immune cell activation, plasma IFNγ, TNFα, IP-10 and MCP-1. Conclusion: PG545 demonstrated a tolerable safety profile, proportional PK, evidence of immune cell stimulation and disease control in some subjects. Taken together, these data support the proposed mechanism of action, which represents a promising approach for use in combination with existing therapies.en© Cancer Research UK 2018Cancer immunotherapy; drug developmentJournal article003008417210.1038/s41416-018-0006-00004300807000032-s2.0-85043460943399931Brown, M. [0000-0002-5796-1932] [0000-0002-6678-1407]